Insulin is a powerful regulator of metabolism. This hormone is important in the regulation of the intermediary metabolism of carbohydrates, proteins, and fats in the liver, adipose tissue, and muscle. Insulin is only synthesized in pancreatic islet beta cells. The most important factor affecting insulin expression in beta cells is the concentration of circulating glucose in the blood, which stimulates insulin secretion, biosynthesis, and transcription. We have shown that the RIPE3b1 and ICE activators act upon sequences of the insulin gene that control glucose.stimulated transcription. We propose to continue our ongoing studies aimed at determining how the RIPE3b1 and ICE activators regulate glucose-induced expression. These studies will concentrate on identifying and characterizing the trans-acting factor(s) from beta cells that appear to bind to RIPE3b1 element sequences and activate insulin gene transcription. We will initially focus on identifying the intracellular signalling events involved in regulating RIPE3b1 and ICE mediated activation during glucose-stimulated transcription. Subsequently, we will investigate the mechanism whereby glucose effects the activity of the RIPE3b1 and ICE activators in beta cells.